# Defining tissue specific phenotypes that faithfully identify tissue resident memory T cells

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2021 · $32,017

## Abstract

ABSTRACT
CD8 T cells control live replicating viral infections, but most licensed vaccines do not efficiently generate
protective memory CD8 T cells. Recent evidence suggests that developing vaccines that establish memory CD8
T cells may be the solution to controlling or preventing historically recalcitrant pathogens. Tissue-resident
memory CD8 T cells (TRM), which occupy many tissues of the body without circulating and persist long term,
have a vital role in tissue immunosurveillance. TRM are also increasingly thought to mediate allergic and
autoimmune responses and transplant rejection. TRM were only recently discovered, and thus there are
substantial gaps in our understanding of the mechanisms by which TRM achieve anti-viral immunity and contribute
to immunopathology. If future vaccination and therapy strategies are to successfully leverage CD8 TRM for
protection against pathogens or reducing immunopathology, fundamental questions on how TRM are generated
and maintained in tissue need to be addressed. I recently compared the transcriptional programs of TRM
populations with recirculating T cell subsets and CD8 T cell populations that transiently express the imperfect
TRM marker CD69 in response to recent TCR stimulation or inflammation. I also developed an original approach
and workflow to identify tissue specific TRM phenotypes. Through Aim 1 I will further expand our knowledge of
shared and tissue specific CD8 TRM transcriptional and phenotypic signatures. I will also validate tissue specific
phenotypes via flow cytometry, parabiosis studies, and the use of `dirty' mice that contain CD69+ T cells within
the equilibrating T cell population. Through Aim 2 I will apply a CRISPR/Cas9 gene editing approach that I have
established to evaluate the role of several exhaustion genes in the ontogeny, differentiation and maintenance of
TRM. Further elucidation of how tissue-resident memory T-cell populations are generated and maintained in
peripheral tissues and the role they play in immune responses in tissue will assist in the design of prophylactic
vaccines and may also inform the development of therapies that treat intractable infections or disease.

## Key facts

- **NIH application ID:** 10313844
- **Project number:** 1F31AI152353-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Milcah C Scott
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,017
- **Award type:** 1
- **Project period:** 2021-07-06 → 2023-07-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313844

## Citation

> US National Institutes of Health, RePORTER application 10313844, Defining tissue specific phenotypes that faithfully identify tissue resident memory T cells (1F31AI152353-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10313844. Licensed CC0.

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